Enantiomeric effects on excitation-contraction coupling in frog skeletal muscle by a chiral phenoxy carboxylic acid.
Aromatic monocarboxylic acids are known to significantly potentiate the mechanical response of skeletal muscle fibers. In this study we investigated the effects of enantiomers of 2-(4-chlorophenoxy)propionic acid, chemically one of the simplest aromatic monocarboxylic acids with chiral properties, on mechanical threshold and charge movement in frog skeletal muscle. The R(+), but not the S(-), enantiomer lowered rheobase mechanical threshold and shifted charge movement to more negative potentials. The R(+) enantiomer also significantly slowed charge movement kinetics, with pronounced delays of the OFF charge transitions. These effects required high temperature for their production. The stereospecific actions of the R(+) enantiomer are interpreted in terms of a specific interaction of this compound at an anion-sensitive site involved in excitation-contraction coupling, most likely on the dihydropryidine-sensitive voltage sensor in the T-system.
Heiny
J A
JA
Department of Physiology and Biophysics, University of Cincinnati, Ohio 45267-0576.
Jong
D
D
Bryant
S H
SH
Conte-Camerino
D
D
Tortorella
V
V
D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D006016:Glycolates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007536:Isomerism; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D011892:Rana catesbeiana; D013329:Structure-Activity Relationship
D006016:Glycolates; C048213:2-(4-chlorophenoxy)propionic acid; D008456:2-Methyl-4-chlorophenoxyacetic Acid